Malaise, Muriel and Rovira, Jordi and Renner, Philipp and Eggenhofer, Elke and Sabet-Baktach, Manije and Lantow, Margareta and Lang, Sven A. and Koehl, Gudrun E. and Farkas, Stefan A. and Loss, Martin and Agha, Ayman and Campistol, Josep M. and Schlitt, Hans J. and Geissler, Edward K. and Kroemer, Alexander (2014) KLRG1(+) NK Cells Protect T-bet-Deficient Mice from Pulmonary Metastatic Colorectal Carcinoma. JOURNAL OF IMMUNOLOGY, 192 (4). pp. 1954-1961. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
We studied the developmental and functional mechanisms behind NK cell-mediated antitumor responses against metastatic colorectal carcinoma (CRC) in mice. In particular, we focused on investigating the significance of T-box transcription factors and the immunotherapeutic relevance of IL-15 in the development and function of tumor-reactive NK cells. Pulmonary CRC metastases were experimentally seeded via an adoptive i. v. transfer of luciferase-expressing CT26 CRC cells that form viewable masses via an in vivo imaging device; genetically deficient mice were used to dissect the antitumor effects of developmentally different NK cell subsets. IL-15 precomplexed to IL-15 receptor-alpha was used in immunotherapy experiments. We found that mice deficient for the T-box transcription factor T-bet lack terminally differentiated antitumor CD27(low) KLRG1(+) NK cells, leading to a terminal course of rapid-onset pulmonary CRC metastases. The importance of this NK cell subset for effective antitumor immunity was shown by adoptively transferring purified CD27(low) KLRG1(+) NK cells into T-bet-deficient mice and, thereby, restoring immunity against lung metastasis formation. Importantly, immunity to metastasis formation could also be restored in T-bet-deficient recipients by treating mice with IL-15 precomplexed to IL-15 receptor-alpha, which induced the development of eomesodermin(+) KLRG1(+) NK cells from existing NK cell populations. Thus, contingent upon their T-bet-dependent development and activation status, NK cells can control metastatic CRC in mice, which is highly relevant for the development of immunotherapeutic approaches in the clinic.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; HELIX INHIBITOR ID2; ANTITUMOR-ACTIVITY; COLON-CANCER; KEY ROLE; IL-15; HOMEOSTASIS; MATURATION; MODEL; INTERLEUKIN-15; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Nov 2019 14:55 |
| Last Modified: | 26 Nov 2019 14:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10668 |
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